Synthesis,self‐assembly,drug‐release behavior,and cytotoxicity of triblock and pentablock copolymers composed of poly(ε‐caprolactone), poly(L‐lactide), and poly(ethylene glycol)

Biocompatible and biodegradable ABC and ABCBA triblock and pentablock copolymers composed of poly(ε‐caprolactone) (PCL), poly(L ‐lactide) (PLA), and poly(ethylene glycol) (PEO) with controlled molecular weights and low polydispersities were synthesized by a click conjugation between alkyne‐terminated PCL‐b‐PLA and azide‐terminated PEO. Their molecular structures, physicochemical and self‐assembly properties were thoroughly characterized by means of FT‐IR, ¹H‐NMR, gel permeation chromatography, differential scanning calorimetry, wide‐angle X‐ray diffraction, dynamic light scattering, and transmission electron microscopy. These copolymers formed microphase‐separated crystalline materials in solid state, where the crystallization of PCL block was greatly restricted by both PEO and PLA blocks. These copolymers self‐assembled into starlike and flowerlike micelles with a spherical morphology, and the micelles were stable over 27 days in aqueous solution at 37 °C. The doxorubicin (DOX) drug‐loaded nanoparticles showed a bigger size with a similar spherical morphology compared to blank nanoparticles, demonstrating a biphasic drug‐release profile in buffer solution and at 37 °C. Moreover, the DOX‐loaded nanoparticles fabricated from the pentablock copolymer sustained a longer drug‐release period (25 days) at pH 7.4 than those of the triblock copolymer. The blank nanoparticles showed good cell viability, whereas the DOX‐loaded nanoparticles killed fewer cells than free DOX, suggesting a controlled drug‐release effect. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Synthesis of linear and star‐like poly(ε‐caprolactone)‐b‐poly{γ‐2‐[2‐(2‐methoxy‐ethoxy)ethoxy]ethoxy‐ε‐caprolactone} amphiphilic block copolymers using zinc undecylenate

Linear and star‐like amphiphilic diblock copolymers were synthesized by the ring‐opening polymerization of ε‐caprolactone and γ‐2‐[2‐(2‐methoxyethoxy)ethoxy]ethoxy‐ε‐caprolactone monomers using zinc undecylenate as a catalyst. These polymers have potential applications as micellar drug delivery vehicles, therefore the properties of the linear and 4‐arm star‐like structures were examined in terms of their molecular weight, viscosity, thermodynamic stability, size, morphology, and drug loading capacity. Both the star‐like and linear block copolymers showed good thermodynamic stability and degradability. However, the star‐like polymers were shown to have increased stability at lower concentrations with a critical micelle concentration (CMC) of 5.62 × 10^?4 g L^?1, which is less than half the concentration of linear polymer needed to form micelles. The star‐like polymeric micelles showed smaller sizes when compared with their linear counterparts and a higher drug loading capacity of doxorubicin, making them better suited for drug delivery purposes. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3601–3608     

Synthesis,micellar structures,and multifunctional sensory properties of poly(3‐hexylthiophene)‐block‐poly(2‐(dimethylamino)ethyl methacrylate) rod‐coil diblock copolymers

We report the synthesis, micellar structures, and multifunctional sensory properties of new conjugated rod‐coil block copolymers, poly(3‐hexylthiophene)‐block‐poly(2‐(di methylamino)ethylmethacrylate)(P3HT‐b‐PDMAEMA). The new copolymers, synthesized by atom transfer radical polymerization of P3HT macroinitiator, consisted PDMAEMA coil lengths of 43, 65, and 124 repeating units. All the P3HT‐b‐PDMAEMA copolymers exhibit a similar low critical solution temperature in water around 33 °C. The micellar structures of the synthesized polymers were characterized by AFM, TEM, and dynamic light scattering, by varying temperature, pH, and water/THF composition. The micelles of P3HT₂₀‐b‐PDMAEMA₄₃ in water had a reversible size change from 75 ± 5 nm to 132 ± 5 nm on heating from 25 to 55 °C and reduced to the original size during cooling. In addition, the micellar size also showed a significant pH dependence, changing from 67 ± 8 nm (pH = 12) to 222 ± 6 nm (pH = 4), depending on the protonation of the PDMAEMA blocks and their electrostatic repulsion. The micellar structure of three P3HT‐b‐PDMAEMA copolymers changed from spheres, to vesicles, and finally to larger sphere micelles as the solvent composition varied from 0 to 100 wt % water in the mixed solvent. The different micellar structures of P3HT₂₀‐b‐PDMAEMA₄₃ solution led to a red‐shift on the absorption or photoluminescence spectra and exhibited the emission colors of yellow, orange, red, and dark red with increasing the water content. This study suggested that new copolymers had potential applications as multifunctional sensory materials toward temperature, pH, and solvent. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Phase‐transition characteristics of amphiphilic poly(2‐ethyl‐2‐oxazoline)/poly(ε‐caprolactone) block copolymers in aqueous solutions

Amphiphilic diblock and triblock copolymers of various block compositions based on hydrophilic poly(2‐ethyl‐2‐oxazoline) (PEtOz) and hydrophobic poly(ε‐caprolactone) were synthesized. The micelle formation of these block copolymers in aqueous media was confirmed by a fluorescence technique and dynamic light scattering. The critical micelle concentrations ranged from 35.5 to 4.6 mg/L for diblock copolymers and 4.7 to 9.0 mg/L for triblock copolymers, depending on the block composition. The phase‐transition behaviors of the block copolymers in concentrated aqueous solutions were investigated. When the temperature was increased, aqueous solutions of diblock and triblock copolymers exhibited gel–sol transition and precipitation, both of which were thermally reversible. The gel–sol transition‐ and precipitation temperatures were manipulated by adjustment of the block composition. As the hydrophobic portion of block copolymers became higher, a larger gel region was generated. In the presence of sodium chloride, the phase transitions were shifted to a lower temperature level. Sodium thiocyanate displaced the gel region and precipitation temperatures to a higher temperature level. The low molecular weight saccharides, such as glucose and maltose, contributed to the shift of phase‐transition temperatures to a lower temperature level, where glucose was more effective than maltose in lowering the gel–sol transition temperatures. The malonic acid that formed hydrogen bonds with the PEtOz shell of micelles was effective in lowering phase‐transition temperatures to 1.0M, above which concentration the block copolymer solutions formed complex precipitates. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 2400–2408, 2000     

Melt crystallization and morphology of poly(ε‐caprolactone)‐poly(ethylene glycol) diblock copolymers with different compositions and molecular weights

Ring opening polymerization of ε‐caprolactone was realized in the presence of monomethoxy poly(ethylene glycol) with M_n = 1000 and 2000, using Zn(La)₂ as catalyst. The resulting PCL‐PEG diblock copolymers with CL/EO repeat unit molar ratios from 0.2 to 3.0 were characterized by using DSC, WAXD, SEC, and ¹H NMR. The crystal phase of PCL blocks exist in all polymers, and the crystallization ability of PCL blocks increases with CL/EO ratio. PEG blocks are able to crystallize for copolymers with CL/EO below 1.0 only. Melt crystallization results were analyzed with Avrami equation. The Averami exponent n is around 3.0 in most cases, in agreement with heterogeneous nucleation with three dimensional growth. The morphology of the crystals was observed by using POM. Rod‐like crystals were found to grow in 1, 3 or 2, 4 quadrants for samples with low molecular weights. In the case of a copolymer with M_n,PEG = 2000 and M_n,PCL = 800, PEG blocks could crystallize and grow on PCL crystals after PCL finished to form rod‐like crystals, leading to formation of poorly or well structured spherulites. The spherulite growth rate (G) was determined at different crystallization temperatures (T_c) ranging from 9 to 49 °C. All the copolymers present a steady G decrease with increasing crystallization temperature due to lower undercooling. On the other hand, increase of CL/EO ratio leads to increase of G in the same T_c range. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 286–293, 2010     

Well‐defined polyolefin/poly(ε‐caprolactone) diblock copolymers: New synthetic strategy and application

A new synthetic strategy, the combination of living polymerization of ylides and ring‐opening polymerization (ROP), was successfully used to obtain well‐defined polymethylene‐b‐poly(ε‐caprolactone) (PM‐b‐PCL) diblock copolymers. Two hydroxyl‐terminated polymethylenes (PM‐OH, M_n= 1800 g mol^?1 (PDI = 1.18) and M_n = 6400 g mol^?1 (PDI = 1.14)) were prepared using living polymerization of dimethylsulfoxonium methylides. Then, such polymers were successfully transformed to PM‐b‐PCL diblock copolymers by using stannous octoate as a catalyst for ROP of ε‐caprolactone. The GPC traces and ¹H NMR of PM‐b‐PCL diblock copolymers indicated the successful extension of PCL segment (M_n of PM‐b‐PCL = 5200–10,300 g mol^?1; PDI = 1.06–1.13). The thermal properties of the double crystalline diblock copolymers were investigated by differential scanning calorimetry (DSC). The results indicated that the incorporation of crystalline segments of PCL chain effectively influence the crystalline process of PM segments. The low‐density polyethylene (LDPE)/PCL and LDPE/polycarbonate (PC) blends were prepared using PM‐b‐PCL as compatibilizer, respectively. The scanning electron microscopy (SEM) observation on the cryofractured surface of such blend polymers indicates that the PM‐b‐PCL diblock copolymers are effective compatibilizers for LDPE/PCL and LDPE/PC blends. Porous films were fabricated via the breath‐figure method using different concentration of PM‐b‐PCL diblock copolymers in CH₂Cl₂ under a static humid condition. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Novel Amphiphilic Degradable Poly(ε‐caprolactone)‐graft‐poly(4‐vinyl pyridine), Poly(ε‐caprolactone)‐graft‐poly(dimethylaminoethyl methacrylate) and Water‐Soluble Derivatives

New amphiphilic graft copolymers that have a poly(ε‐caprolactone) (PCL) biodegradable hydrophobic backbone and poly(4‐vinylpyridine) (P4VP) or poly(2‐(N,N‐dimethylamino)ethyl methacrylate) (PDMAEMA) hydrophilic side chains have been prepared by anionic polymerization of the corresponding 4VP and DMAEMA monomers using a PCL‐based macropolycarbanion as initiator. The water solubility of these amphiphilic copolymers is improved by quaternization, which leads to fully water‐soluble cationic copolymers that give micellar aggregates in deionized water with diameters ranging from 65 to 125 nm. In addition, to improve the hydrophilicity of PCL‐g‐P4VP, grafting of poly(ethylene glycol) (PEG) segments has been carried out to give a water‐soluble double grafted PCL‐g‐(P4VP;PEG) terpolymer.

     

Synthesis and aggregation of poly(valine)‐poly (ethylene glycol) block copolymers

The solubility nature of many medicines presents a challenge for successful delivery of these drugs to the body. Polymeric carriers are potentially viable as vessels for both the protection and transport of these medicinal substances. In an effort to generate polymeric materials for this desired application, A‐B‐A triblock copolymers have been synthesized with a central block composed of hydrophilic poly (ethylene glycol) (PEG) and flanking hydrophobic sequences composed of five valine units terminated with end groups of varying hydrophobicity. These copolymers were constructed by adding amino acids stepwise to the hydrophilic block using solution phase chemistry. The self‐assembly behavior of all polymers was investigated using fluorimetry with a pyrene probe. In general, copolymers with more hydrophobic end groups exhibited lower critical aggregation concentrations (CACs). Fmoc‐terminated copolymers displayed the lowest CAC of 0.032 mg/mL and demonstrated little cytotoxicity when exposed to SW620 colorectal cancer cells. Transmission electron micrographs show the presence of multiple compartments within these spherical assemblies, which may prove useful in encapsulating medicinal substances. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5381–5389, 2008     

Amphiphilic block copolymers of high‐molecular‐weight poly(ethylene oxide) and either ε‐caprolactone or γ‐methyl‐ε‐caprolactone: Synthesis and characterization

Ethylene oxide (EO) has been block‐polymerized with both ε‐caprolactone (ε‐CL) and γ‐methyl‐ε‐caprolactone (MCL) through the combination of the anionic polymerization of EO and the ring‐opening polymerization (ROP) of ε‐CL and MCL. ω‐Hydroxyl poly(ethylene oxide) has been reacted with triethylaluminum (OH/Al = 1) and converted into a macroinitiator for ROP of ε‐CL and MCL. In toluene at room temperature, this polymerization leads to a bimodal molecular weight distribution as a result of monomer insertion in only some of the aluminum alkoxide bonds. However, in a more polar solvent (methylene chloride) added with 1 equiv of a Lewis base (pyridine), the expected diblock is formed selectively, and this indicates that aggregation of the active species in toluene is responsible for a macroinitiator efficiency of less than 1. A series of amphiphilic diblock copolymers with poly(ε‐caprolactone) (semicrystalline) and poly(γ‐methyl‐ε‐caprolactone) (amorphous) as the hydrophobic blocks have been prepared and characterized with size exclusion chromatography, ¹H NMR, IR, and wide‐angle X‐ray scattering. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1132–1142, 2004     

Synthesis and characterization of biodegradable A–B–A triblock copolymers containing poly(ϵ‐caprolactone) A blocks and poly(trans‐4‐hydroxy‐L‐proline) B blocks

Novel, biodegradable poly(?‐caprolactone)‐block‐poly(trans‐4‐hydroxy‐N‐benzyloxycarbonyl‐L ‐proline)‐block‐poly(?‐caprolactone) triblock copolymers were synthesized by ring‐opening polymerization from dihydroxyl‐terminated macroinitiator poly(trans‐4‐hydroxy‐N‐benzyloxycarbonyl‐L ‐proline) (PHpr) and ?‐caprolactone (?‐CL) with stannous octoate as the catalyst. The molecular weights were characterized with gel permeation chromatography and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. With an increase in the contents of ?‐CL incorporated into the copolymers, a decrease in the glass‐transition temperature (T_g) was observed. The T_g values of copoly(4‐phenyl‐?‐caprolactone) and copoly(4‐methyl‐?‐caprolactone) were higher than T_g of copoly(?‐caprolactone). Their micellar characteristics in an aqueous phase were investigated with fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy. The block copolymers formed micelles in the aqueous phase with critical micelle concentrations in the range of 1.00–1.36 mg L^?1. With higher molecular weights and hydrophobic components in the copolymers, a higher critical micelle concentration was observed. As the feed weight ratio of antitriptyline hydrochloride (AM) to the polymer increased, the drug loading increased. The micelles exhibited a spherical shape, and the average size was less than 250 nm. The in vitro hydrolytic degradation and controlled drug release properties of the triblock copolymers were also investigated. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4268–4280, 2006     

Synthesis and micellization of star‐like hyperbranched polymer with poly(ethylene oxide) and poly(ε‐caprolactone) arms

Novel star‐like hyperbranched polymers with amphiphilic arms were synthesized via three steps. Hyperbranched poly(amido amine)s containing secondary amine and hydroxyl groups were successfully synthesized via Michael addition polymerization of triacrylamide (TT) and 3‐amino‐1,2‐propanediol (APD) with feed molar ratio of 1:2. ¹H, ¹³C, and HSQC NMR techniques were used to clarify polymerization mechanism and the structures of the resultant hyperbranched polymers. Methoxyl poly(ethylene oxide) acrylate (A‐MPEO) and carboxylic acid‐terminated poly(ε‐caprolactone) (PCL) were sequentially reacted with secondary amine and hydroxyl group, and the core–shell structures with poly(1TT‐2APD) as core and two distinguishing polymer chains, PEO and PCL, as shell were constructed. The star‐like hyperbranched polymers have different sizes in dimethyl sulfonate, chloroform, and deionized water, which were characterized by DLS and ¹H NMR. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1388–1401, 2008     

Preparation of poly(ethylene oxide)‐block‐poly(isoprene) by nitroxide‐mediated free radical polymerization from PEO macroinitiators

Amphiphilic poly(ethylene oxide)‐block‐poly(isoprene) (PEO‐b‐PI) diblock copolymers were prepared by nitroxide‐mediated polymerization of isoprene from alkoxyamine‐terminal poly(ethylene oxide) (PEO). PEO monomethyl ether (M_n ≈ 5200 g/mol) was functionalized by esterification with 2‐bromopropionyl bromide with subsequent copper‐mediated replacement of the terminal bromine with 2,2,5‐trimethyl‐4‐phenyl‐3‐azahexane‐3‐nitroxide. The resulting PEO‐alkoxyamine macroinitiator was used to initiate polymerization of isoprene in bulk and in solution at 125 °C to yield PEO‐b‐PI block copolymers with narrow molecular weight distributions (M_w/M_n ≤ 1.1). Polymerizations were first order in isoprene through 35% conversion. Micellar aggregates of PEO‐b‐PI in aqueous solution were crosslinked by treatment with a water‐soluble redox initiating system, and persistent micellar structures were observed in the dry state by AFM. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2977–2984, 2005     

Bioreducible and core‐crosslinked hybrid micelles from trimethoxysilyl‐ended poly(ε‐caprolactone)‐S‐S‐poly(ethylene oxide) block copolymers: Thiol‐ene click synthesis and properties

Bioreducible and core‐crosslinked hybrid micelles were for the first time fabricated from biodegradable and biocompatible trimethoxysilyl‐terminated and disulfide‐bond‐linked block copolymers poly(ε‐caprolactone)‐S‐S‐poly(ethylene oxide), which were prepared by combining thiol‐ene coupling reaction and ring‐opening polymerization. The molecular structures, physicochemical, self‐assembly, and bioreducible properties of these copolymers were thoroughly characterized by means of FTIR, ¹H NMR, gel permeation chromatography, differential scanning calorimetry, wide‐angle X‐ray diffraction, dynamic light scattering (DLS), and transmission electron microscopy. The core‐crosslinking sol‐gel reaction was confirmed by ¹H NMR, and the core‐crosslinked hybrid micelles contained about 3 wt % of silica. The bioreducible property of both uncrosslinked and core‐crosslinked micelles in 10 mM 1,4‐dithiothreitol (DTT) solution was monitored by DLS, which demonstrated that the PEO corona gradually shedded from the PCL core. The anticancer doxorubicin drug‐loaded micelles showed nearly spherical morphology compared with blank micelles, presenting a DTT reduction‐triggered drug‐release profile at 37 °C. Notably, the core‐crosslinked hybrid micelles showed about twofold drug loading capacities and a half drug‐release rate compared with the uncross‐liked counterparts. This work provides a useful platform for the fabrication of bioreducible and core‐crosslinked hybrid micelles potential for anticancer drug delivery system. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

The Influence of Pendant Hydroxyl Groups on Enzymatic Degradation and Drug Delivery of Amphiphilic Poly[glycidol‐block‐(ε‐caprolactone)] Copolymers

An amphiphilic diblock copolymer PG‐b‐PCL with well‐controlled structure and pendant hydroxyl groups along hydrophilic block was synthesized by sequential anionic ring‐opening polymerization. The micellization and drug release of PG‐b‐PCL copolymers using pyrene as a fluorescence probe were investigated for determining the influences of copolymer composition and lipase concentration on drug loading capacity and controlled release behavior. The biodegradation of PG‐b‐PCL copolymers was studied with microspheres as research samples. It has been concluded that the polar hydroxyl groups along each repeat unit of hydrophilic PG block in PG‐b‐PCL copolymer have great influences on drug encapsulation, drug release, and enzymatic degradation of micelles and microspheres.

     

pH‐sensitive polymeric micelles based on amphiphilic polypeptide as smart drug carriers

A series of amphiphilic diblock copolymers having poly(ethylene glycol) (PEG) as one block and a polypeptide as the other block were synthesized by ring‐opening polymerization using PEG‐amine as a macroinitiator. These polymers were characterized by ¹H‐NMR and gel permeation chromatography. The influence of the substitution ratio of tertiary amine‐containing groups on the pH sensitivity of the polymers was investigated in detail. Core/shell‐structured micelles were fabricated from these polymers using an organic solvent‐free method. pH‐ and concentration‐dependent micellization behaviors were investigated by dynamic light scattering and fluorescence microscopy. Micelles loaded with doxorubicin, selected as a model drug, showed restricted drug release at physiological pH but accelerated drug release at tumor extracellular pH. Collectively, our findings suggest that these pH‐sensitive micelles might have great potential for cancer therapy applications. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 4175–4182     

Amphiphilic gradient copolymers of 2‐methyl‐ and 2‐phenyl‐2‐oxazoline: self‐organization in aqueous media and drug encapsulation

Gradient (or pseudo‐diblock) copolymers were synthesized from 2‐methyl‐2‐oxazoline and 2‐phenyl‐2‐oxazoline monomer mixtures via cationic polymerization. The self‐assembling properties of these biocompatible gradient copolymers in aqueous solutions were investigated, in an effort to use the produced nanostructures as nanocarriers for hydrophobic pharmaceutical molecules. Dynamic and static light scattering as well as AFM measurements showed that the copolymers assemble in different supramolecular nanostructures (spherical micelles, vesicles and aggregates) depending on copolymer composition. Fluorescence spectroscopy studies revealed a microenvironment of unusually high polarity inside the nanostructures. This observation is related partly to the gradient structure of the copolymers. The polymeric nanostructures were stable with time. Their structural properties in different aqueous media—PBS buffer, RPMI solution—simulating conditions used in pharmacological/medicinal studies, have been also investigated and a composition dependent behavior was observed. Finally, the hydrophobic drug indomethacin was successfully encapsulated within the gradient copolymer nanostructures and the properties of the mixed aggregates were studied in respect to the initial copolymer assemblies. The produced aggregates encapsulating indomethacin showed a significant increase of their mass and size compared to original purely polymeric ones. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis and bulk characterization of new P(CB‐b‐S) diblock copolymers

Strongly asymmetric chlorinated polybutadiene‐b‐polystyrene, [P((CB)_x‐b‐(PS)_y)] diblock copolymers with increasing x/(x + y) ratios (up to 5.2 mol %) have been synthesized by the selective chlorination of the polybutadiene (PB) block in solution. Chlorination has been performed in anhydrous dichloromethane added with an antioxidant [2,2′‐methylenebis‐(6‐tert‐butyl‐4‐methyl‐phenol)], at −50°C, under a continuous Ar flow and in the dark. Under the optimized experimental conditions, the PB chlorination is not complete, but the PS block is left unmodified. Even in the presence of a large chlorine excess (Cl₂/butene unit molar ratio of 2.5), the experimental degree of chlorination of homo PB does not exceed 85%. The chlorinated copolymers have been characterized by ¹H‐NMR, IR spectroscopy, size‐exclusion chromatography, and elemental analysis. The chlorinated copolymers have also been studied by DSC and SAXS after annealing at 150°C. Although at this temperature the parent homopolymers are immiscible, no microphase separation has been observed for the block copolymers. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 233–244, 1999     

Synthesis and characterization of well‐defined,amphiphilic poly(N‐isopropylacrylamide)‐ b‐[2‐hydroxyethyl methacrylate‐poly(ϵ‐caprolactone)]n graft copolymers by RAFT polymerization and macromonomer method

The well‐defined, thermosensitive and biodegradable graft copolymers, poly(N‐isopropylacrylamide)‐b‐[2‐hydroxyethyl methacrylate‐poly(ε‐caprolactone)]_n (PNIPAAm‐b‐(HEMA‐PCL)_n) (n = 3 or 9), were synthesized by combining reversible addition‐fragmentation chain transfer polymerization and macromonomer method. The copolymers were able to self‐assemble into micelles in water with low critical micellar concentration and demonstrated temperature sensitivity with a lower critical solution temperature at around 36 °C. Transmission electron microscopy shows that the micelles exhibit a nanosized spherical morphology within a size range of 30–100 nm. The PNIPAAm‐b‐(HEMA‐PCL)₃ copolymer exhibited biodegradation and low cytotoxicity. The paclitaxel‐loaded PNIPAAm‐b‐(HEMA‐PCL)₃ micelles displayed thermosensitive controlled release behavior, which indicates potential as drug carriers. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5354–5364, 2007     

Synthesis,self‐assembly and recognition properties of biomimetic star‐shaped poly(ε‐caprolactone)‐b‐glycopolymer block copolymers

Biomimetic star‐shaped poly(ε‐caprolactone)‐b‐poly(gluconamidoethyl methacrylate) block copolymers (SPCL‐PGAMA) were synthesized from the atom transfer radical polymerization (ATRP) of unprotected GAMA glycomonomer using a tetra(2‐bromo‐2‐methylpropionyl)‐terminated star‐shaped poly(ε‐caprolactone) (SPCL‐Br) as a macroinitiator in NMP solution at room temperature. The block length of PGAMA glycopolymer within as‐synthesized SPCL‐PGAMA copolymers could be adjusted linearly by controlling the molar ratio of GAMA glycomonomer to SPCL‐Br macroinitiator, and the molecular weight distribution was reasonably narrow. The degree of crystallization of PCL block within copolymers decreased with the increasing block length ratio of outer PGAMA to inner PCL. Moreover, the self‐assembly properties of the SPCL‐PGAMA copolymers were investigated by NMR, UV‐vis, DLS, and TEM, respectively. The self‐assembled glucose‐installed aggregates changed from spherical micelles to worm‐like aggregates, then to vesicles with the decreasing weight fraction of hydrophilic PGAMA block. Furthermore, the biomolecular binding of SPCL‐PGAMA with Concanavalin A (Con A) was studied by means of UV‐vis, fluorescence spectroscopy, and DLS, which demonstrated that these SPCL‐PGAMA copolymers had specific recognition with Con A. Consequently, this will not only provide biomimetic star‐shaped SPCL‐PGAMA block copolymers for targeted drug delivery, but also improve the compatibility and drug release properties of PCL‐based biomaterials for hydrophilic peptide drugs. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 817–829, 2008